PT-141 (Bremelanotide)

Bremelanotide (PT-141) is a synthetic cyclic heptapeptide that acts as a non-selective agonist of melanocortin receptors, with activity at MC1R, MC4R, MC3R, MC5R, and MC2R in descending order of potency. The MC4R pathway in the central nervous system — particularly in the hypothalamus — is considered most relevant to its effects on sexual desire and arousal, distinguishing its mechanism from phosphodiesterase-5 (PDE5) inhibitors like sildenafil, which act peripherally on vascular smooth muscle. PT-141 addresses the central (CNS) component of sexual response rather than the peripheral vascular component.¹

Bremelanotide was developed by Palatin Technologies over more than a decade of clinical research, originally from a serendipitous observation that an earlier melanocortin compound (melanotan II) produced spontaneous erections in a clinical pharmacology study. PT-141 is the refined, cyclic peptide derivative. It received FDA approval in 2019 under the brand name Vyleesi, manufactured by AMAG Pharmaceuticals (subsequently acquired by other parties).¹

Vyleesi (bremelanotide injection) is FDA-approved for:

• Treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not attributable to a co-existing medical or psychiatric condition, relationship problems, or the effects of a medication or substance.¹

Important limitations from the FDA label:

• Not indicated for treatment of HSDD in postmenopausal women.
• Not indicated for use in men.
• Not indicated to enhance sexual performance.

Off-label use: Bremelanotide is used off-label in men for hypoactive sexual desire and erectile dysfunction, particularly in men who have not responded adequately to PDE5 inhibitors or for whom PDE5 inhibitors are contraindicated. This use is not FDA-approved but is legally prescribable by a physician.

The FDA-approved dose is 1.75 mg administered as a single subcutaneous injection to the abdomen or thigh, taken as needed approximately 45 minutes before anticipated sexual activity. No more than one dose should be taken within 24 hours. The label advises that more than 8 doses per month is not recommended due to the potential for cumulative hyperpigmentation.¹

Subcutaneous injection via single-dose prefilled autoinjector (Vyleesi). Compounded forms (nasal spray, sublingual lozenge) are available through some prescribers as off-label alternatives for patients who prefer not to inject; these are not FDA-approved formulations.

Store at or below 25°C (77°F). Do not freeze. Protect from light.¹

Key warnings and considerations from the FDA label:¹

• Transient blood pressure increase and heart rate decrease: Following injection, transient increases in blood pressure (mean peak increase approximately 6 mmHg systolic) and decreases in heart rate typically occur and resolve within 12 hours. Bremelanotide is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease due to this effect. Blood pressure should be well-controlled before use.
• Nausea: The most common adverse effect, occurring in approximately 40% of women in clinical trials. Nausea typically begins approximately 1 hour after injection, peaks at approximately 1–3 hours, and resolves within 12 hours. An antiemetic taken 1 hour before injection can reduce this effect.
• Hyperpigmentation: Focal hyperpigmentation (darkening) of the face, gums, and breasts has been reported with repeated use. This effect is dose- and frequency-dependent and may be permanent. The 8-doses-per-month recommendation is partly driven by this concern.
• Flushing: Hot flush/flushing is reported in approximately 20% of women in clinical trials.
• Pregnancy: May cause fetal harm based on animal studies. Discontinue if pregnancy occurs.¹